All complex multicellular animals sense gravity and use this sensory information to generate coherent locomotor responses. Gravitational sensing mechanisms have been investigated in many animal systems, but to date, there has been no systematic application of a genetic approach to this problem. The long-term objective of the proposed research is to use a genetic approach to dissect out the gravitational response mechanisms operating in the model organism Drosophila melanogaster. Given the broad evolutionary conservation of molecular signaling pathways already established in eukaryotes, mechanisms identified in Drosophila are likely to be directly relevant to human gravitational responses. We have developed behavioral paradigms based on the use of gravitaxic mazes for detecting aberrant gravitaxic responses in Drosophila. Using, these assays, we have identified at least 50 mutant strains with altered gravitaxic behavior. For approximately half of these strains, the location of the mutation responsible for the gravitaxic phenotype has been determined and for 14 strains, the gene affected by the mutation has been preliminarily identified. The specific aims for the immediate future include genetic complementation/mapping studies, behavioral studies and gene expression studies that will define more exactly the lesions associated with the various mutations. Modeling studies of the behavior in the gravitaxic mazes is also planned in addition to the development of simpler gravitaxic assays that could be used in microgravity. By coordinating information from these various experimental routes for the individual gravitaxic mutants we will be able to address the following questions. i) Which regions of the central nervous system are used to process and coordinate gravitational information? ii) Which peripheral sense organs are used to sense gravity? iii) What role does light play in modulating gravitaxic responses? iv) What molecular signaling pathways are used in the processing of gravitational information in the peripheral and central nervous systems?